Normal-appearing white matter in patients with phenylketonuria: water content, myelin water fraction, and metabolite concentrations.

Abstract

To prospectively assess relative water content (RWC), myelin water fraction (MWF), and hydrogen 1 magnetic resonance (MR) spectroscopy findings in the white matter (WM) of patients with phenylketonuria (PKU). This study was approved by the institution's investigational review board, and informed consent was obtained. T2 water relaxation data were acquired by using a 48-echo measurement in a transverse plane through the genu and splenium of the corpus callosum in 16 patients (six men, 10 women; age range, 18-40 years) with PKU and 16 age- and sex-matched control subjects. MR spectroscopy was performed in a voxel (94x70x15 mm) above the ventricles. WM in control subjects (defined as normal WM) was compared with normal-appearing WM (NAWM) and diffuse WM lesions in patients with PKU by using a Student t test. Patients with PKU had two forms of NAWM: (a) areas that looked normal on intermediate-weighted (IW) and T2-weighted MR images and long T2 maps and (b) areas that looked normal on IW and T2-weighted MR images but were hyperintense on long T2 maps. Both forms of NAWM showed increased RWC (up to 2.5%, P<.001) and reduced MWF (up to 56%, P<.001) relative to normal WM; these changes paralleled those seen in diffuse WM lesions. Approximately 9% of the water in diffuse WM lesions was in a reservoir with a long T2 time of 200-800 msec. Myoinositol concentrations were reduced by 14% (P=.003) in patients with PKU. In patients with PKU, NAWM and diffuse WM lesions have altered RWC and MWF relative to normal WM, and diffuse WM lesions show a redistribution of water into an extracellular reservoir with a long T2 time.